Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre‐ and post‐natal exposure to moderate levels of ethanol

González-Burgos, Ignacio; Alejandre-Gómez, Misael

doi:10.1016/j.ijdevneu.2004.11.002

Cited by 29 publications

(13 citation statements)

References 28 publications

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“…Though the cerebellar Purkinje cells are of particular interest given their position in cerebellar circuitry, ethanol can also lead to loss and dysfunction of other cerebellar neurons, as well as many glial populations including the Bergmann glia (Dikranian et al, 2005; Gonzalez-Burgos and Alejandre-Gomez, 2005). In fact, administration of ethanol during the early postnatal period can lead to reductions of cerebellar granule cells (Bonthius and West, 1990; Goodlett and Eilers, 1997; Hamre and West, 1993), deep cerebellar nuclei (Green et al, 2002) and the inferior olivary nucleus (Napper and West, 1995), as well as neurodegeneration of cerebellar-related neurons in the brainstem (Dikranian et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Administration of Memantine During Ethanol Withdrawal in Neonatal Rats: Effects on Long-Term Ethanol-Induced Motor Incoordination and Cerebellar Purkinje Cell Loss

Idrus

McGough

Riley

et al. 2010

Alcoholism: Clinical and Experimental Research

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Background Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g. MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine if administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Methods Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10 or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Results Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Conclusions Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders.

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Section: Discussionmentioning

confidence: 99%

Administration of Memantine During Ethanol Withdrawal in Neonatal Rats: Effects on Long-Term Ethanol-Induced Motor Incoordination and Cerebellar Purkinje Cell Loss

Idrus

McGough

Riley

et al. 2010

Alcoholism: Clinical and Experimental Research

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“…For example, ethanol exposure affects the development and functions of glia (Miller and Robertson, 1993;Gonzalez-Burgos and Alejandre-Gomez, 2005), which in turn may alter granule cell motility. To determine whether alcohol directly affects the migration of granule cells, we used microexplant cultures of P0 -P3 mouse cerebella (Komuro and Rakic, 1996;Yacubova and Komuro, 2002a,b).…”

Section: Direct Action Of Ethanol On the Intrinsic Migratory Behaviormentioning

confidence: 99%

Reversal of Neuronal Migration in a Mouse Model of Fetal Alcohol Syndrome by Controlling Second-Messenger Signalings

Kumada¹,

Lakshmana²,

Komuro³

2006

J. Neurosci.

131

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The brains of fetal alcohol syndrome patients exhibit impaired neuronal migration, but little is known about the mechanisms underlying this abnormality. Here we show that Ca 2ϩ signaling and cyclic nucleotide signaling are the central targets of alcohol action in neuronal cell migration. Acute administration of ethanol reduced the frequency of transient Ca 2ϩ elevations in migrating neurons and cGMP levels and increased cAMP levels. Experimental manipulations of these second-messenger pathways, through stimulating Ca 2ϩ and cGMP signaling or inhibiting cAMP signaling, completely reversed the action of ethanol on neuronal migration in vitro as well as in vivo. Each second messenger has multiple but distinct downstream targets, including Ca 2ϩ /calmodulin-dependent protein kinase II, calcineurin, protein phosphatase 1, Rho GTPase, mitogen-activated protein kinase, and phosphoinositide 3-kinase. These results demonstrate that the aberrant migration of immature neurons in the fetal brain caused by maternal alcohol consumption may be corrected by controlling the activity of these second-messenger pathways.

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“…Ethanol exposure during this period inhibits the migration of CGC from the EGL to the IGL (107). Interestingly, prenatal ethanol exposure also delays the migration of CGC during the postnatal period, indicating that prenatal exposure to ethanol is sufficient to disrupt the neuronal migration program (108). Similarly, de la Monte et al (2009) show CGC isolated from prenatal rats exposed to ethanol display impaired migration in vitro (109).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Ethanol-Induced Death of Cerebellar Granule Cells

Luo

2010

Cerebellum

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Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system (CNS) underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that is most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of NMDA receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis.

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Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre‐ and post‐natal exposure to moderate levels of ethanol

Cited by 29 publications

References 28 publications

Administration of Memantine During Ethanol Withdrawal in Neonatal Rats: Effects on Long-Term Ethanol-Induced Motor Incoordination and Cerebellar Purkinje Cell Loss

Administration of Memantine During Ethanol Withdrawal in Neonatal Rats: Effects on Long-Term Ethanol-Induced Motor Incoordination and Cerebellar Purkinje Cell Loss

Reversal of Neuronal Migration in a Mouse Model of Fetal Alcohol Syndrome by Controlling Second-Messenger Signalings

Mechanisms of Ethanol-Induced Death of Cerebellar Granule Cells

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